This invention relates generally to a method and apparatus for extracorporeal blood treatment. More particularly, the invention provides a method and apparatus for treating certain disease states by way of an extracorporeal circuit capable of simultaneously and/or intermittently carrying out three separate treatment modalities.
The invention has particular utility in the treatment of human beings who have been infected with Human Immunodeficiency Virus-Type 1 (HIV-1) and will be discussed herein with particular reference thereto. HIV-1 has previously been known by several names including AIDS-related virus (ARV), Human T-Lymphotropic Virus-Type 3 (HTLV-3), and Lymphadenopathy-Associated Virus (LAV). The HIV-1 is associated with virtually all presently reported AIDS cases in the United States. It is noted, however, that a second HIV variant, known as Human Immunodeficiency Virus-Type 2 (HIV-2) has also been identified. HIV-2 shares similar biological properties with HIV-1 and is known to cause AIDS in certain regions of Central Africa. Thus, it is probable that the particular therapeutic efficacy of the present invention will extend to other AIDS-inducing viruses in addition to HIV-1 as well as to other immune disorders. Accordingly, as used herein, the term HIV-1 shall not be construed as a limiting or narrowing of the therapeutic applicability of the invention in any way.
A number of prior art devices are known for carrying out extracorporeal treatment of the blood. Indeed, many extracorporeal treatment methods have become well established as routine methods of treating specific conditions or diseases Examples of extracorporeal treatment methods of known effectiveness include those adapted for extracorporeal blood oxygenation, plasmapheresis, leukapheresis, membrane dialysis, electrodialysis, radiotherapy, and extracorporeal treatment by various pharmacological and chemotherapeutic agents.
Specific examples of extracorporeal blood treatment devices and methods are described in U.S. Pat. Nos. 2,886,771 (Vincent); 4,321,918 (Clark II); 4,322,275 (Jain); 4,381,004 (Babb); 3,482,575 (Claff et al.); 4,479,798 (Parks); 4,540,401 (Marten); 4,563,170 (Aigner); 4,576,143 (Clark III); and 4,692,138 (Troutner et al.).
In particular, U.S. Pat. No. 3,482,575 (Claff et al) discloses an extracorporeal blood oxygenation method wherein sodium bicarbonate is added to adjust the pH of the blood to 7.45-7.50 or higher prior to oxygenation. Such alkalization of the blood is purported to enable the blood to take up a greater amount of oxygen during the ensuing extracorporeal oxygenation process.
U.S. Pat. No. 4,692,138 (Troutner et al.) discloses a pump block which is used to interface an irradiation chamber with a roller pump. Such pump block is incorporated into an extracorporeal apparatus wherein photoactivatable agents are added to the patient's blood prior to extracorporeal irradiation of the blood. After such irradiation is completed, the blood is returned to the patient.
U.S. Pat. Nos. 4,321,918 and 4,576,143 (Clark II and Clark III) disclose a process and method of extracorporeally irradiating whole blood to alter lymphocyte function (Clark II) and to modify the immune response in humans affected with immune disorders (Clark III).
U.S. Pat. No. 4,479,798 (Parks) describes a subcutaneously implantable device for warming the blood so as to raise the patient's core temperature to 41.5.degree.-42.5.degree. C. for the purpose of hyperthermically retarding the growth of cancer cells within the body.
Also, U.S. Pat. No. 4,381,004 (Babb) describes a method for treating infectious and parasitic diseases whereby the patient's blood, or a fraction thereof, is treated extracorporeally with a biologically or pharmacologically active agent capable of inactivating the target microorganism. Thereafter, the inactivating agent is scavenged or removed from the blood prior to returning the blood to the patient. The Babb system is purported to allow the use of chemical or biological drugs which, at the doses required, would exhibit toxic or other adverse effects if administered directly to the patient.
Also, U.S. Pat. No. 4,540,401 (Marten) describes a means and method for removing immunoreactive compounds from blood using immunological homologes of the compound bound to the surfaces of lipid vesicles.
None of these extracorporeal methods and devices of the prior art have been specifically designed for the treatment of blood infected with the HIV-1. Given the present incurability of Acquired Immune Deficiency Syndrome (AIDS) and the widely predicted capacity of the disease to reach widespread epidemic proportions, there exists a compelling need for a means of extracorporeally inhibiting or destroying the blood borne HIV-1 while preserving the physiological integrity and compatibility of the blood so that it may be returned to the patient following treatment. Thus, the present invention is intended to fill such compelling need.
The HIV-1 virus, like many retroviruses, is known to be temperature labile. In fact, the HIV-1 virus has been reported to undergo thermal inactivation in certain in vitro preparations at relatively moderate temperatures. McDougal, J. S. et al., Thermal Inactivation of Acquired Immunodeficiency Syndrome Virus, Human T-Lymphotropic Virus-III/Lymphadenopathy-Associated Virus, With Special Reference to Antihemophilic Factor, Journal of Clinical Investigation, 76:875-877 (August, 1985) and Spire, B. et al., Inactivation of Lymphadenopathy-Associated Virus By Heat, Gamma Rays, and Ultraviolet Light; Lancet:188-189 (Jan. 26, 1985).
Also, it is suspected that T-lymphocytes which contain or have been infected by the HIV-1 virus may become structurally fragile. The possible fragility of HIV-1 infected cells suggests that such cells may be selectively disrupted or destroyed within an extracorporeal circuit by the induction of mechanical shear or be more sensitive to temperature and/or PO.sub.2 increases or decreases or other physical agents described herein.
In addition, helium-neon and helium-cadmium laser irradiation, at certain wavelengths, has been reported to have certain immunostimulative and immunosuppressive effects on human lymphocytes in vitro. Kupin, V. I. et al., The Effect of Nondamaging Intensity Laser Irradiation on the Immune System, Neoplasma 34:3, 325-330 (1987). Other types of radiant energy within the electromagnetic spectrum are also known to have immunosuppressive/immunostimulative effects Ultraviolet radiation has been reported to cause immunosuppresive effects which may prevent certain T-lymphocytes from being drawn to the HIV-1 virus. Horowitz, J., et al., Selective T Cell Killing of Human Lymphocytes by Ultraviolet Radiation; Cellular Immunology, 14:80-86 (1974). X-rays and other types of radiant energy may also have effects on the blood constituents and/or infecting organisms or viruses.
Thus, based on the present state of knowledge respecting the HIV-1 virus, applicant has identified firm scientific foundation for the provision of a novel, single extracorporeal device capable of intermittently or simultaneously utilizing (a) hyperthermia of the blood, (b) selective mechanical damage to virally affected cells, and (c) irradiation (preferably laser and/or UV and/or x-ray) as means of treating HIV-1 infected persons.